CD38‐Specific Gallium‐68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET

• Published in: Advanced science Vol. 11; no. 16; pp. e2308617 - n/a
• Main Authors: Sharma, Ajay Kumar, Gupta, Kuldeep, Mishra, Akhilesh, Lofland, Gabriela, Marsh, Ian, Kumar, Dhiraj, Ghiaur, Gabriel, Imus, Philip, Rowe, Steven P., Hobbs, Robert F., Gocke, Christian B., Nimmagadda, Sridhar
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01-04-2024; John Wiley and Sons Inc; Wiley
• Subjects: Antigens; ATRA; Biodistribution; Bone marrow; Cancer therapies; CD38; daratumumab; Drug dosages; isatuximab; Liver; Molecular weight; Monoclonal antibodies; Multiple myeloma; Peptides; PET; Pharmacodynamics; Pharmacokinetics; Tomography; Tumors; isatuximab; CD38; ATRA; daratumumab; pharmacodynamics; PET
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202308617

The limited availability of molecularly targeted low‐molecular‐weight imaging agents for monitoring multiple myeloma (MM)‐targeted therapies has been a significant challenge in the field. In response, a first‐in‐class peptide‐based radiotracer, [68Ga]Ga‐AJ206, is developed that can be seamlessly integrated into the standard clinical workflow and is specifically designed to noninvasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). A bicyclic peptide, AJ206, is synthesized and exhibits high affinity to CD38 (KD: 19.1 ± 0.99 × 10−9 m) by surface plasmon resonance. Further, [68Ga]Ga‐AJ206‐PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [68Ga]Ga‐AJ206 detects CD38 expression in cell line‐derived xenografts, patient‐derived xenografts (PDXs), and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68Ga]Ga‐AJ206‐PET successfully quantifies CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following all‐trans retinoic acid (ATRA) therapy. In conclusion, [68Ga]Ga‐AJ206 exhibits the salient features required for clinical translation, providing CD38‐specific high‐contrast images in multiple models of MM. [68Ga]Ga‐AJ206‐PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.
A novel peptide‐based gallium‐68 labeled radiotracer, [68Ga]Ga‐AJ206, is developed for imaging multiple myeloma using positron emission tomography (PET). [68Ga]Ga‐AJ206 delivers PET images with high contrast within 60 min and detected varying levels of CD38 expression with high sensitivity (left panel). Furthermore, [68Ga]Ga‐AJ206‐PET enables noninvasive quantification of CD38 pharmacodynamics (right panel).